Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China (mainland).
Department of Cardiology, Tianjin Haihe Hospital, Tianjin, China (mainland).
Med Sci Monit. 2019 Feb 7;25:1038-1045. doi: 10.12659/MSM.913106.
BACKGROUND Contrast-induced acute kidney injury is an important clinical problem, yet its pathogenic mechanisms are incompletely understood. In this study we explored the potential beneficial effects of probucol as treatment of contrast-induced acute kidney injury in diabetic rats. MATERIAL AND METHODS Rats were divided into 3 groups: i) diabetic control, ii) diabetic with contrast, and iii) probucol treatment groups. Probucol was administered by gavage and the contrast diatrizoate (60%) was injected via femoral vein. After 24 h, the rats were sacrificed and samples were taken to measure biochemical indicators. Pathological damage of renal tubules was evaluated by HE staining. Expression of Bcl-2, Bax, p-ERKs, and p-JNK proteins in the kidneys was examined by Western blotting, whereas expression level of caspase-3 in kidneys was detected by immunohistochemistry. RESULTS Compared to the probucol treatment group, the diabetes with contrast group showed higher serum creatinine and lower creatinine clearance. The pathological changes of kidneys in the probucol treatment group were improved compared with the contrast group. Moreover, Western blot analyses revealed that use of contrast agent led to lower p-ERK1/2, higher p-JNK, lower Bcl-2, and higher Bax levels, which were reversed by probucol. Finally, immunohistochemical findings revealed higher caspase-3 after contrast use, which was partially reversed by probucol. CONCLUSIONS Probucol exerts protective effects on contrast-induced acute kidney injury in diabetic rats by inhibition of renal cell apoptosis. This is achieved by reducing mitochondrial caspase-3 expression through increasing and decreasing the expression of the upstream mediators p-ERK1/2 and p-JNK, respectively.
对比剂诱导的急性肾损伤是一个重要的临床问题，但它的发病机制尚不完全清楚。在这项研究中，我们探讨了普罗布考作为糖尿病大鼠对比剂诱导急性肾损伤治疗的潜在有益作用。
大鼠分为 3 组：i）糖尿病对照组，ii）糖尿病伴对比剂组，iii）普罗布考治疗组。普罗布考通过灌胃给药，二碘酞酸（60%）通过股静脉注射。24 小时后，处死大鼠并取样本测量生化指标。通过 HE 染色评估肾小管的病理损伤。通过 Western blot 检测肾脏中 Bcl-2、Bax、p-ERK 和 p-JNK 蛋白的表达，通过免疫组化检测肾脏中 caspase-3 的表达水平。
与普罗布考治疗组相比，糖尿病伴对比剂组的血清肌酐升高，肌酐清除率降低。普罗布考治疗组的肾脏病理变化较对比组改善。此外，Western blot 分析显示，使用对比剂导致 p-ERK1/2 降低，p-JNK 升高，Bcl-2 降低，Bax 升高，而普罗布考可逆转这些变化。最后，免疫组化结果显示，使用对比剂后 caspase-3 升高，而普罗布考可部分逆转。
普罗布考通过抑制肾细胞凋亡对糖尿病大鼠对比剂诱导的急性肾损伤发挥保护作用。这是通过增加和减少上游介质 p-ERK1/2 和 p-JNK 的表达来实现的，从而分别降低线粒体 caspase-3 的表达。
